Marplan

Name: Marplan

Uses of Marplan

Marplan is a prescription medication used to treat depression, when other medications have failed.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Marplan Precautions

Serious side effects have been reported with Marplan including:

Hypertensive crisis, a life threatening increase in blood pressure. This sometimes fatal side effect can result from taking MAO inhibitors like Marplan with certain drugs and foods (see "Drug Interactions" and "Food Interactions" sections). Symptoms include:

  • headaches
  • stiff or sore neck
  • nausea
  • vomiting
  • palpitations
  • sweating, sometimes with fever and cold, clammy skin
  • either fast or slow heart beat
  • chest pain
  • chest tightness
  • dilated pupils

Get medical help right away if you experience these symptoms.

Severe headaches. If you have frequent headaches, talk to your doctor before starting Marplan as headaches are one of the first symptoms of a hypertensive crisis and you may miss this warning sign.

Suicidal thoughts or behavior. Antidepressants may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment. 

  • Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
  • Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.

Low blood pressure, especially when getting up from a lying position.

Worsening of seizures in people with epilepsy. Before taking Marplan, tell your doctor if you have epilepsy.

Do not take Marplan if you:

  • are allergic to any ingredient in Marplan 
  • have heart disease
  • have high blood pressure
  • have a type of adrenal tumor known as pheochromocytoma
  • have a history of a stroke
  • have had a transient ischemic attack (TIA)
  • have had bleeding in the brain
  • are going to have surgery 
  • have liver disease
  • are taking drugs that should not be taken during treatment with Marplan 

Marplan can cause drowsiness. Do not drive or operate heavy machinery until you know how it affects you.

 

Marplan Usage

  • Take Marplan exactly as prescribed.
  • Marplan comes in tablet form and is taken 2 to 4 times a day.
  • It can be taken with or without food.
  • If Marplan upsets your stomach, try taking it with food.
  • If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Marplan at the same time.
  

Marplan Overdose

If you take too much Marplan, call your local Poison Contol Center or seek emergency medical attention right away.

What is the most important information I should know about Marplan (isocarboxazid)?

There are many other medicines that can cause serious medical problems or death if you take them together with isocarboxazid. Before taking isocarboxazid, tell your doctor about all medicines you have used within the past 5 weeks.

Do not use isocarboxazid if you have used another MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include linezolid, methylene blue injection, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine, and others.

Some young people have thoughts about suicide when first taking an antidepressant. Your doctor will need to check your progress at regular visits while you are using isocarboxazid. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

While you are taking isocarboxazid, you must not drink alcohol or eat foods that are high in tyramine, listed in the "What should I avoid while taking isocarboxazid?" section of this leaflet. Eating tyramine while you are taking isocarboxazid can raise your blood pressure to dangerous levels.

What should I discuss with my doctor before taking Marplan (isocarboxazid)?

You should not take isocarboxazid if you are allergic to it, or if you have:

  • pheochromocytoma (tumor of the adrenal gland);

  • liver disease;

  • kidney disease;

  • a history of stroke or blood clots;

  • heart disease, high blood pressure; or

  • a history of severe or frequent headaches.

There are many other medicines that can cause serious medical problems or death if you take them together with isocarboxazid.

Before taking isocarboxazid, tell your doctor about all medicines you have used within the past 5 weeks. The following drugs should not be used while you are taking isocarboxazid:

  • buspirone (Buspar);

  • carbamazepine;

  • levodopa;

  • methyldopa;

  • tryptophan;

  • certain antidepressants--amitriptylline, bupropion, citalopram, clomipramine, desipramine, doxepin, escitalopram, fluoxetine, fluvoxamine, imipramine, maprotiline, nortriptyline, paroxetine, protriptyline, sertraline, trimipramine (known by brand names such as Celexa, Lexapro, Luvox, Norpramin, Prozac, Paxil, Wellbutrin, and Zoloft);

  • narcotic pain medicine--morphine, tramadol, Demerol, OxyContin, Percocet, Vicodin, and others;

  • ADHD medicine--Adderall, Concerta, Ritalin, Vyvanse, and others;

  • diet pills; or

  • over-the-counter cough or cold medicine.

Do not use isocarboxazid if you have used another MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include linezolid, methylene blue injection, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine, and others.

To make sure isocarboxazid is safe for you, tell your doctor if you have:

  • a history of heart disease or high blood pressure;

  • diabetes;

  • a thyroid disorder;

  • schizophrenia;

  • epilepsy or other seizure disorder; or

  • if you have taken any other antidepressant within the past 5 weeks.

Some young people have thoughts about suicide when first taking an antidepressant. Your doctor will need to check your progress at regular visits while you are using isocarboxazid. Your family or other caregivers should also be alert to changes in your mood or symptoms.

FDA pregnancy category C. It is not known whether isocarboxazid will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether isocarboxazid passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Do not give isocarboxazid to anyone younger than 16 years old without the advice of a doctor.

Precautions While Using Marplan

It is very important that your doctor check your progress at regular visits to allow for changes in your dose and to check for any unwanted effects.

You will also need to have your blood pressure measured before starting this medicine and while you are using it. If you notice any change to your normal blood pressure, call your doctor right away. If you have questions about this, talk to your doctor.

When taken with certain foods, drinks, or other medicines, isocarboxazid can cause very dangerous reactions, such as sudden high blood pressure (also called hypertensive crisis). To avoid such reactions, follow these rules of caution:

  • Do not eat foods that have dopamine and a high tyramine content (most common in foods that are aged or fermented to increase their flavor), such as cheese (especially strong or aged kinds), caviar, sour cream, liver, canned figs, soy sauce, sauerkraut, fava beans, yeasts, and yogurt. Avoid smoked or pickled meat, poultry, or fish, such as sausage, pepperoni, salami, anchovies, or herring. Do not eat dried fruit (such as raisins), bananas, avocados, raspberries, or very ripe fruit.
  • Do not drink alcoholic beverages. This includes Chianti wine, sherry, beer, non-alcohol or low alcohol beer and wine, and liqueurs.
  • Do not eat or drink too much caffeine. Caffeine can be found in coffee, cola, chocolate, tea, and many other foods and drinks. Ask your doctor how much caffeine is safe to use.

Isocarboxazid may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you or your caregiver notice any of these adverse effects, tell your doctor right away.

Call your doctor or hospital emergency room right away if you have a severe headache, stiff or sore neck, chest pains, fast heartbeat, sweating, dizziness, or nausea and vomiting while you are taking this medicine. These may be symptoms of a serious side effect called hypertensive crisis.

This medicine may make some people dizzy or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; medicine for seizures or barbiturates; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.

Dizziness, lightheadedness, or fainting may occur, especially when you get up suddenly from a lying or sitting position. Getting up slowly may help. When you get up from lying down, sit on the edge of the bed with your feet dangling for 1 or 2 minutes, then stand up slowly. If the problem continues or gets worse, check with your doctor.

Do not stop taking this medicine without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely.

Before having any kind of surgery, dental treatment, or emergency treatment, tell the medical doctor or dentist in charge that you are using this medicine or have used it within the past 10 days. Taking isocarboxazid together with medicines that are used during surgery, dental, or emergency treatments may increase the risk of serious side effects.

Your doctor may want you to carry an identification card stating that you are using this medicine.

Check with your doctor right away if you have any symptoms of liver problems, such as dark-colored urine or pale stools, nausea, vomiting, loss of appetite, pain in your upper stomach, or yellowing of your skin or the whites of your eyes.

This medicine may affect blood sugar levels. If you are diabetic, be especially careful in testing for sugar in your blood or urine. If you have any questions about this, check with your doctor.

After you stop using this medicine, you must continue to exercise caution for at least 2 weeks with your foods, drinks, and other medicines, since these items may continue to react with isocarboxazid.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

What are some things I need to know or do while I take Marplan?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists. This medicine may need to be stopped before certain types of surgery as your doctor has told you. If Marplan is stopped, your doctor will tell you when to start taking this medicine again after your surgery or procedure.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how Marplan affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • High blood pressure has happened with this medicine. Sometimes, this has been deadly. Have your blood pressure checked as you have been told by your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Some foods and drinks like cheese and red wine, when taken with Marplan, may cause very risky effects such as sudden high blood pressure. To avoid these problems, get a list of foods to avoid.
  • If this medicine is stopped, follow diet for at least 2 more weeks.
  • If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
  • Do not take Marplan with other drugs for low mood (depression), diet pills, stimulants like amphetamines, reserpine, or pain drugs without talking with your doctor. There needs to be some time between stopping one drug and starting the other. Talk with your doctor about all the drugs you take.
  • Do not use OTC drugs that have dextromethorphan or pseudoephedrine. They may cause very high blood pressure when used with this medicine.
  • If you are taking Marplan (isocarboxazid) and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
  • Avoid alcohol or other drugs and natural products that slow your actions.
  • This medicine may raise the chance of seizures in some people, including people who have had seizures in the past. Talk to your doctor to see if you have a greater chance of seizures while taking this medicine.
  • Limit your use of caffeine (for example, tea, coffee, cola) and chocolate. Use with Marplan may cause nervousness, shakiness, and a fast heartbeat.
  • Do not give to a child younger than 16 years of age.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Marplan - Clinical Pharmacology

Pharmacodynamics

Isocarboxazid is a non-selective hydrazine monoamine oxidase (MAO) inhibitor. In vivo and in vitro studies demonstrated inhibition of MAO in the brain, heart, and liver. The mechanism by which MAO inhibitors act as antidepressants is not fully understood, but it is thought to involve the elevation of brain levels of biogenic amines. However, MAO is a complex enzyme system, widely distributed throughout the body, and drugs that inhibit MAO in the laboratory are associated with a number of clinical effects. Thus, it is unknown whether MAO inhibition per se, other pharmacologic actions, or an interaction of both is responsible for the antidepressant effects observed.

Pharmacokinetics

Marplan pharmacokinetic information is not available.

Clinical Efficacy Data

The effectiveness of Marplan was demonstrated in two 6-week placebo-controlled studies conducted in adult outpatients with depressive symptoms that corresponded to the DSM-IV category of major depressive disorder. The patients often also had signs and symptoms of anxiety (anxious mood, panic, and/or phobic symptoms). Patients were initiated with a dose of 10 mg bid, with increases every 2 to 4 days, as tolerated, until a therapeutic effect was achieved, up to a maximum dose of 80 mg/day. Doses were administered on a divided schedule ranging from 2 to 4 times a day. The mean dose overall for both studies was approximately 40 mg/day, with very few patients receiving doses greater than 60 mg/day. In both studies at the end of 6 weeks, patients receiving Marplan had significantly greater reduction in signs and symptoms of depression evaluated by the Hamilton Depression Scale, for both the Total Score and the Depressed Mood Score, than patients who received placebo.

Precautions

Information for Patients

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Marplan and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medications, Depression and Other Serious Mental Illness, and Suicidal Thoughts and Actions” is available for Marplan. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have.  The complete text of the Medication Guide is reprinted at the end of this document.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Marplan.

Clinical Worsening and Suicide Risk

Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.

Pediatric Use-Safety and effectiveness in the pediatric population have not been established (see BOX WARNING and WARNINGS-Clinical Worsening and Suicide Risk).

Anyone considering the use of Marplan in a child or adolescent must balance the potential risks with the clinical need.

General

Hypotension

Hypotension has been observed during Marplan therapy. Symptoms of postural hypotension are seen most commonly, but not exclusively, in patients with preexistent hypertension; blood pressure usually returns rapidly to pretreatment levels upon discontinuation of the drug. Dosage increases should be made more gradually in patients showing a tendency toward hypotension at the beginning of therapy. Postural hypotension may be relieved by having the patient lie down until blood pressure returns to normal. When Marplan is combined with phenothiazine derivatives or other compounds known to cause hypotension, the possibility of additive hypotensive effects should be considered.

Lower Seizure Threshold

Because Marplan lowers the convulsive threshold in some animal experiments, suitable precautions should be taken if epileptic patients are treated. Marplan appears to have varying effects in epileptic patients; while some have a decrease in frequency of seizures, others have more seizures.

Drugs that lower the seizure threshold, including MAO inhibitors, should not be used with Amipaque® (metrizamide, Sanofi Winthrop Pharmaceuticals). As with other MAO inhibitors, Marplan should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.

Hepatotoxicity

There is a low incidence of altered liver function or jaundice in patients treated with Marplan. In the past, it was difficult to differentiate most cases of drug-induced hepatocellular jaundice from viral hepatitis although this is no longer true. Periodic liver chemistry tests should be performed during Marplan therapy; use of the drug should be discontinued at the first sign of hepatic dysfunction or jaundice.

Suicide

In depressed patients, the possibility of suicide should always be considered and adequate precautions taken. Exclusive reliance on drug therapy to prevent suicidal attempts is unwarranted, as there may be a delay in the onset of therapeutic effect or an increase in anxiety or agitation. Also, some patients fail to respond to drug therapy or may respond only temporarily. The strictest supervision, and preferably hospitalization, are required.

Use in Patients With Concomitant Illness

MAO inhibitors can suppress anginal pain that would otherwise serve as a warning of myocardial ischemia.

In patients with impaired renal function, Marplan should be used cautiously to prevent accumulation.

Some MAO inhibitors have contributed to hypoglycemic episodes in diabetic patients receiving insulin or glycemic agents. Marplan should therefore be used with caution in diabetics using these drugs.

Marplan may aggravate coexisting symptoms in depression, such as anxiety and agitation.

Use Marplan with caution in hyperthyroid patients because of their increased sensitivity to pressor amines.

Marplan should be used cautiously in hyperactive or agitated patients, as well as in schizophrenic patients, because it may cause excessive stimulation. Activation of mania/hypomania has been reported in a small proportion of patients with major affective disorder who were treated with marketed antidepressants.

Drug Interactions

See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS sections for information on drug interactions.

Marplan should be administered with caution to patients receiving Antabuse® (disulfiram, Wyeth-Ayerst Laboratories). In a single study, rats given high intraperitoneal doses of an MAO inhibitor plus disulfiram experienced severe toxicity, including convulsions and death.

Concomitant use of Marplan and other psychotropic agents is generally not recommended because of possible potentiating effects. This is especially true in patients who may subject themselves to an overdosage of drugs. If combination therapy is needed, careful consideration should be given to the pharmacology of all agents to be used. The monoamine oxidase inhibitory effects of Marplan may persist for a substantial period after discontinuation of the drug, and this should be borne in mind when another drug is prescribed following Marplan. To avoid potentiation, the physician wishing to terminate treatment with Marplan and begin therapy with another agent should allow for an interval of 10 days.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies to evaluate carcinogenic potential have not been conducted with this drug, and there is no information concerning mutagenesis or impairment of fertility.

Pregnancy Category C

The potential reproductive toxicity of isocarboxazid has not been adequately evaluated in animals. It is also not known whether isocarboxazid can cause embryo/fetal harm when administered to a pregnant woman or can affect reproductive capacity. Marplan should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Levels of excretion of isocarboxazid and/or its metabolites in human milk have not been determined, and effects on the nursing infant are unknown. Marplan should be used in women who are nursing only if clearly needed.

Pediatric Use

Marplan is not recommended for use in patients under 16 years of age, as safety and effectiveness in pediatric populations have not been demonstrated.

Marplan Dosage and Administration

For maximum therapeutic effect, the dosage of Marplan must be individually adjusted on the basis of careful observation of the patient. Dosage should be started with one tablet (10 mg) of Marplan twice daily. If tolerated, dosage may be increased by increments of one tablet (10 mg) every 2 to 4 days to achieve a dosage of four tablets daily (40 mg) by the end of the first week of treatment. Dosage can then be increased by increments of up to 20 mg/week, if needed and tolerated, to a maximum recommended dosage of 60 mg/day. Daily dosage should be divided into two to four dosages. After maximum clinical response is achieved, an attempt should be made to reduce the dosage slowly over a period of several weeks without jeopardizing the therapeutic response. Beneficial effect may not be seen in some patients for 3 to 6 weeks. If no response is obtained by then, continued administration is unlikely to help.

Because of the limited experience with systematically monitored patients receiving Marplan at the higher end of the currently recommended dose range of up to 60 mg/day, caution is indicated in patients for whom a dose of 40 mg/day is exceeded (see ADVERSE REACTIONS).

Principal display panel

NDC 30698-032-01

Marplan®
(isocarboxazid)
10 mg
100 Tablets
Rx Only   

Marplan 
isocarboxazid tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:30698-032
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ISOCARBOXAZID (ISOCARBOXAZID) ISOCARBOXAZID 10 mg
Inactive Ingredients
Ingredient Name Strength
LACTOSE  
STARCH, CORN  
POVIDONE  
D&C RED NO. 27  
FD&C YELLOW NO. 6  
MAGNESIUM STEARATE  
Product Characteristics
Color ORANGE (peach) Score 2 pieces
Shape ROUND (ROUND) Size 8mm
Flavor Imprint Code Marplan;10
Contains     
Packaging
# Item Code Package Description
1 NDC:30698-032-01 100 TABLET in 1 BOTTLE, PLASTIC
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA011961 07/01/1959
Labeler - Validus Pharmaceuticals LLC (801194619)
Revised: 06/2016   Validus Pharmaceuticals LLC
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